Communication

Genetic Incorporation of Multiple Unnatural Amino Acids into Proteins in Mammalian Cells^†

Han Xiao

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/

These authors contributed equally to this work.

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Dr. Abhishek Chatterjee,

Dr. Abhishek Chatterjee

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/

These authors contributed equally to this work.

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Dr. Sei-hyun Choi,

Dr. Sei-hyun Choi

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/

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Dr. Krishna M. Bajjuri,

Dr. Krishna M. Bajjuri

Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)

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Prof. Dr. Subhash C. Sinha,

Prof. Dr. Subhash C. Sinha

Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)

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Prof. Dr. Peter G. Schultz,

Corresponding Author

Prof. Dr. Peter G. Schultz

[email protected]

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/Search for more papers by this author

Han Xiao,

Han Xiao

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/

These authors contributed equally to this work.

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Dr. Abhishek Chatterjee,

Dr. Abhishek Chatterjee

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/

These authors contributed equally to this work.

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Dr. Sei-hyun Choi,

Dr. Sei-hyun Choi

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/

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Dr. Krishna M. Bajjuri,

Dr. Krishna M. Bajjuri

Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)

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Prof. Dr. Subhash C. Sinha,

Prof. Dr. Subhash C. Sinha

Department of Cell and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)

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Prof. Dr. Peter G. Schultz,

Corresponding Author

Prof. Dr. Peter G. Schultz

[email protected]

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) http://schultz.scripps.edu/

First published: 08 November 2013

https://doi.org/10.1002/anie.201308137

Citations: 174

^†

We acknowledge Virginia Seely for her assistance in manuscript preparation. We thank Dr. Jun Y. Axup and Dr. Chan Hyuk Kim for helpful discussions. This is manuscript no. 25034 from The Scripps Research Institute. This work was funded by grant DE-FG03-00ER46051 from the Division of Materials Sciences, Department of Energy to P.G.S.

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Graphical Abstract

An enhanced suppression system enables the expression of proteins in mammalian cells incorporating one unnatural amino acid (UAA) into multiple sites, as well as two different UAAs into distinct sites in a protein of interest. The utility of this technology was demonstrated by generating a full-length antibody, site-specifically conjugated to a drug and a fluorophore, and characterizing its activity in vitro (see picture).

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Volume52, Issue52

December 23, 2013

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Genetic Incorporation of Multiple Unnatural Amino Acids into Proteins in Mammalian Cells^†

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Genetic Incorporation of Multiple Unnatural Amino Acids into Proteins in Mammalian Cells^†